Batch vs. continuous direct compression – a comparison of material processability and final tablet quality

Abstract

In this study, an in-depth comparison was made between batch and continuous direct compression using similar compression set-ups. The overall material processability and final tablet quality were compared and evaluated. Correlations between material properties, process parameters and final tablet properties were made via multivariate data analyses. In total, 10 low-dosed (1% w/w) and 10 high-dosed (40% w/w) formulations were processed, using a total of 10 different fillers/filler combinations. The trials indicated that the impact of filler type, drug load or process settings was similar for batch and continuous direct compression. The main differentiator between batch and continuous was the flow dynamics in the operating system, where properties related to flow, compressibility and permeability played a crucial role. The less consistent flow throughout a batch process resulted in a significantly higher variability within the tablet press (σCF) and for the tablet quality responses (σMass, σTS). However, the better controlled blending procedure prior to batch processing was reflected in a more consistent API concentration variability. Overall, the comparison showed the benefits of selecting appropriate excipients and process settings to achieve a specific outcome, keeping in mind some key differentiators between both processes.

Keywords

• Continuous manufacturing
• Direct compression
• Excipients
• Raw material characterization
• Material scinece
• Multivariate analysis